Inhibitory Effect of TRK-530 on Inflammatory Cytokines in Bone Marrow of Rats with Adjuvant Arthritis

Tanahashi, Masahiko; Koike, Jyunzo; Kawabe, Norio; Nakadate-Matsushita, Teruo

doi:10.1159/000028203

Cited by 13 publications

(11 citation statements)

References 17 publications

(16 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have shown that TRK-530 can prevent rat adjuvant arthritis that might be the result of a decrease in inflammatory cytokines such as TNF-α and neutrophil chemoattractant (CINC)-1. A decrease in serum sialic acid, a systemic parameter of inflammation, has also been reported in TRK-530-treated animals with adjuvant arthritis (7,8). Based on these findings, we have been studying the effect of this compound on PGE 2 synthesis in organ culture of neonatal mouse calvaria.…”

Section: Inhibitory Effect On the Synthesis Of Pgementioning

confidence: 70%

Pharmacological Topics of Bone Metabolism: A Novel Bisphosphonate for the Treatment of Periodontitis

et al. 2008

View full text Add to dashboard Cite

Abstract. It has been reported that the pharmacological characteristics of bisphosphonates vary depending on the side chain attached to the carbon atom of the P-C-P bond. TRK-530 is a novel synthetic bisphosphonate with an anti-oxidant methylthio-phenylthio side chain. This compound has been suggested to have both anti-inflammatory and anti-bone-resorbing effects. Such a compound could be effective for the treatment of diseases with excessive bone resorption accompanied by inflammation. We have been studying this compound as a potential therapeutic agent for periodontitis. To date, we have found that 1) TRK-530 inhibited osteoclastic bone resorption in animals and in bone organ culture, 2) both systemic and topical administration of TRK-530 prevented alveolar bone loss in animals with experimental periodontitis, 3) TRK-530 prevented prostaglandin E 2 synthesis by inhibiting the expression of cyclooxygenase (COX)-2 mRNA, and 4) TRK-530 inhibited the formation of dental calculus. The above results suggest that TRK-530 might be useful for the treatment of alveolar bone loss in periodontitis.

show abstract

Section: Inhibitory Effect On the Synthesis Of Pgementioning

confidence: 70%

Pharmacological Topics of Bone Metabolism: A Novel Bisphosphonate for the Treatment of Periodontitis

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Here we observed an increase in serum sialic acid, a marker of rheumatoid arthritis (29), in GAS-infected mice. Experimental rats with adjuvant arthritis showed a similar increase in serum sialic acid (32). Therefore, some common mechanisms may underlie both septic arthritis and rheumatoid arthritis.…”

Section: Vol 71 2003 Gas Induces Septic Arthritis With Increased Ramentioning

confidence: 85%

“…Certain bacterial virulence factors such as superantigens and exotoxins have been implicated in S. aureus arthritis (33), and host immune responses were reported to be important in the induction and progression of this disease (12,32,35). Inflammatory cytokines such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor alpha (TNF-␣) participate in the pathogenesis of septic arthritis (4).…”

mentioning

confidence: 99%

Streptococcus pyogenesInfection Induces Septic Arthritis with Increased Production of the Receptor Activator of the NF-κB Ligand

Sakurai¹,

Okahashi

Nakagawa³

et al. 2003

Infect Immun

View full text Add to dashboard Cite

Bacterial arthritis is a rapidly progressive and highly destructive joint disease in humans, with Staphylococcus aureus and Neisseria gonorrhoeae the major causative agents, although beta-hemolytic streptococci as well often induce the disease. We demonstrate here that intravenous inoculation of CD-1 mice with the group A streptococcus (GAS) species Streptococcus pyogenes resulted in a high incidence of septic arthritis. Signs of arthritis emerged within the first few days after injection, and bacterial examinations revealed that colonization of the inoculated GAS in the arthritic joints persisted for 21 days. Induction of persistent septic arthritis was dependent on the number of microorganisms inoculated. Immunohistochemical staining of GAS with anti-GAS antibodies revealed colonization in the joints of infected mice. Cytokine levels were quantified in the joints and sera of infected mice by using an enzyme-linked immunosorbent assay. High levels of interleukin-1␤ (IL-1␤) and IL-6 were detected in the joints from 3 to 20 days after infection. We noted that an increase in the amount of receptor activator of NF-B ligand (RANKL), which is a key cytokine in osteoclastogenesis, was also evident in the joints of the infected mice. RANKL was not detected in sera, indicating local production of RANKL in the infected joints. Blocking of RANKL by osteoprotegerin, a decoy receptor of RANKL, prevented bone destruction in the infected joints. These results suggest that GAS can colonize in the joints and induce bacterial arthritis. Local RANKL production in the infected joints may be involved in bone destruction.

show abstract

“…These are the subcutaneous injection of turpentine (Liao et al 1986;Bu¨rger et al 1987;Myers and Fleck 1988;Jinbo et al 2002) and the injection of FCA into the footpad (Sternberg et al 1974;Bu¨rger et al 1987;Connolly et al 1988;Tanahashi et al 1998). However, a third, less frequently used model involving the intraperitoneal (i.p.)…”

Section: Introductionmentioning

confidence: 99%

Markers of experimental acute inflammation in the Wistar Han rat with particular reference to haptoglobin and C-reactive protein

Giffen

Turton

Andrews

et al. 2003

Archives of Toxicology

View full text Add to dashboard Cite

C-reactive protein (CRP), haptoglobin (Hp) and fibrinogen (Fbgn) are acute phase reactants (APRs), the blood levels of which increase during acute inflammation. However, although the levels of these APRs are used to monitor inflammation in man, their usefulness and sensitivity as markers of inflammation in rodents are less clear. We therefore wished to evaluate, in a comparative fashion, a prototype immunoassay for serum CRP, a commercial assay for serum Hp, and an automated assay for Fbgn, using a model of acute inflammation in the rat. Additionally, pro-inflammatory cytokines and serum protein fractions were also measured. The model of inflammation used was the intraperitoneal injection of Freund's complete adjuvant (FCA). In a concluding experiment, findings with Hp in the FCA rat model were validated in a toxicologically relevant study involving the induction of acute hepatic inflammation using the model hepatotoxicant carbon tetrachloride (CCl(4)). Female Wistar Han rats were treated with a single injection of FCA in a dose-response study (1.25-10.0 ml/kg, sampling at 36 h) and two time-course studies (over 40 h and 21 days). In a final experiment, rats were dosed with CCl(4) at 0.8 ml/kg and sampled over a 17-day period. In FCA and CCl(4) experiments, serum/plasma was prepared and tissues taken at autopsy for histological assessment (CCl(4) study only). In the dose-response study, serum CRP, Hp and plasma Fbgn were increased at all FCA dose levels at 36 h post-dosing. Serum alpha(2) and beta(1) globulin fractions were also increased, while albumin levels were decreased. In the 40-h time-course study, CRP levels peaked at 25-40 h post-dosing, to approximately 120% of control (as 100%). Hp levels increased to a maximum at 25 and 40 h post-dosing with values greater than 400% of control, and alpha(2) and beta(1) globulin fractions peaked at 30 and 40 h post-dosing to 221 and 187% of control, respectively. Increased serum interleukin-6 (IL-6) and interleukin-1beta (IL-1beta) levels peaked at 20 h (11-fold) and 25 h (19-fold), respectively. In a 21-day time-course study, no increased CRP levels were measured despite elevated levels of Hp, which peaked at 36 h (approximately 7-fold above control), and remained elevated up to 21 days. IL-6 and IL-1beta levels peaked at 12 h (19-fold) and 24 h (28-fold), respectively. Liver histopathology of animals treated with CCl(4) showed centrilobular hepatocellular degeneration and necrosis (most significant at 36 h) with an inflammatory response (most significant at 48 h). Resolution of the lesion was complete by 4 days post-dosing. Serum alanine aminotransferase, aspartate aminotransferase and glutamate dehydrogenase levels peaked at 36 h post-dosing. Hp levels increased maximally at 48 h (426% of control). We conclude that serum CRP is a poor marker of acute inflammation in the rat in comparison with serum Hp and plasma Fbgn. Between Hp and Fbgn, serum Hp is shown to be the most sensitive and useful marker of acute inflammation.

show abstract

Inhibitory Effect of TRK-530 on Inflammatory Cytokines in Bone Marrow of Rats with Adjuvant Arthritis

Cited by 13 publications

References 17 publications

Pharmacological Topics of Bone Metabolism: A Novel Bisphosphonate for the Treatment of Periodontitis

Pharmacological Topics of Bone Metabolism: A Novel Bisphosphonate for the Treatment of Periodontitis

Streptococcus pyogenesInfection Induces Septic Arthritis with Increased Production of the Receptor Activator of the NF-κB Ligand

Markers of experimental acute inflammation in the Wistar Han rat with particular reference to haptoglobin and C-reactive protein

Contact Info

Product

Resources

About